Journal Article

PUBDB-2025-02287

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Protonated Glutamate and Aspartate Side Chains Can Recognize Phosphodiester Groups via Strong and Short Hydrogen Bonds in Biomacromolecular Complexes

Neißner, K. ; Duchardt-Ferner, E. ; Wiedemann, C. ; Kraus, J. ; Hellmich, U. A. ; Wöhnert, J. (Corresponding author)

2025
Wiley-VCH Weinheim

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Please use a persistent id in citations: doi:10.1002/anie.202501589  doi:10.3204/PUBDB-2025-02287

Abstract: Phosphodiester groups occur ubiquitously in nature, e.g. in nucleic acids or in cyclic (di-)nucleotides important for signal transduction. Proteins often use polar or positively charged amino acids to interact with the negatively charged phosphodiester groups via hydrogen bonds and salt bridges. In contrast, the acidic amino acids aspartate and glutamate are generally not considered as important determinants for phosphodiester group recognition. Instead, they are regarded as detrimental to such interactions due to the assumed charge repulsion between their deprotonated, negatively charged side chain carboxylate groups and the phosphodiester. Accordingly, acidic amino acids are often purposefully introduced into proteins to abrogate nucleic acid interactions in functional studies. Here, we show that in appropriate structural contexts, glutamate side chains are readily protonated even at neutral pH and act as hydrogen bond donors to phosphodiester groups using a c-di-GMP binding protein – the GSPII-B domain of PilF from Thermus thermophilus – as an example. Surveying available RNA-protein and DNA-protein complex structures in the PDB, we found that hydrogen bonds between apparently protonated carboxylate groups of glutamate and aspartate and phosphodiester groups occur frequently in many different functional protein classes. Thus, the functional role of acidic amino acids in phosphodiester group recognition needs to be re-evaluated.

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Contributing Institute(s):

1. EMBL-User (EMBL-User)

Research Program(s):

1. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)
2. DFG project G:(GEPRIS)390713860 - EXC 2051: Balance of the Microverse (390713860) (390713860)

Experiment(s):

1. PETRA Beamline P13 (PETRA III)

Appears in the scientific report 2025

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Database coverage:
; ; ; Chemical Reactions ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 15 ; Index Chemicus ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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